The purpose of this project is to investigate age-related changes in thermoregulation and to examine the physiological mechanisms underlying these changes. We have demonstrated that aged mice have diminished cold tolerance and are not able to adapt to repeated cold exposure. The cause of these age- related aberrations in thermoregulation appears to be, in part, a reduction in metabolic heat production and, in part, a reduction in heat conservation. During the life span, the relative contributions of heat production and heat conservation mechanisms to cold tolerance change. The results from a number of experiments suggest that the mechanism responsible for diminished metabolic heat production in response to cold is an age-related change in brown adipose tissue (BAT). Aged mice have a lower level of thermogenin in BAT at thermo-neutrality and after cold exposure than do adults. However, the response of aged mice to repeated cold exposure by induction of new thermogenin is proportionally as good as is the response of adult animals. Time of day of cold exposure affects cold tolerance: Adult animals produce equal amounts of heat in response to the same degree of cold at different times of day, but their heat conservation mechanisms are much weaker during afternoon testing. Heat conservation mechanisms also appear to be less activated during the afternoon administration of inhalation narcosis.